Neutrophil count that defines neutropenia? (List ranges for mild, moderate, and severe)
Mild: 1000-1500/ µL Moderate: 500-1000/ µL Severe: <500/ µL
What are the general principles that lead to neutropenia?
Decreased production, ineffective production, or increased destruction
List some causes of decreased production of neutrophils
Irradiation, drug induced, viral infection, congenital (Kostmann syndrome or infantile genetic agranulocytosis), cyclic
List causes of ineffective production of neutrophils
Megaloblastic anemia, myelodysplastic syndromes
List causes of increased destruction of neutrophils
isoimmune neonatal, autoimmune, idiopathic, drug induced, Felty syndrome, SLE, dialysis, splenic sequestration, increased margination **BIG PICTURE: 1) too much consumption, like in infection 2) too much sequestration, like in hypersplenism 3) too much Ab destruction
Neutrophil count that defines neutrophilia?
Above 7000/ µL
Causes of neutrophilia?
1) increased mobilization from bone marrow 2) enhanced release from marginal pool 3) stimulation of granulopoiesis
Huge elevation of WBCs, usually in response to acute infections or severe hemorrhage. May be mistaken for leukemia, esp CML. Distinguished by segmented neutrophils, high leukocyte alkaline phosphatase activity, and blue cytoplasmic inclusions (Dohle bodies).
Seen in response to allergic reactions, parasitic infections, or persistent Ag-Ab complexes. Leads to necrosis, especially of myocardium and nervous system.
Eosinophilia - remember major basic protein causes the cell injury!
Commonly observed in immediate-type hypersensitivity reactions and chronic myeloproliferative neoplasms. Think histamine, chondroitin sulfate, leukotrienes.
Often occurs in neutropenic states as a compensatory mechanism
Myeloproliferative neoplasm, derived from abnormal pluripotent stem cell, strong association with Philadelphia chromosome, BCR/ABL, t(9;22)
Chronic Myelogenous Leukemia
Phase of CML associated with lower blasts, normal platelets, hypercellularity in BM, and clusters of megakaryocytes.
Phase of CML associated with increasing WBC count, increasing splenomegaly, persistent thrombocytopenia, and 10-20% blasts
Phase of CML associated with at least 20% blasts, extramedullary proliferation of blasts, clusters of blasts (hint: ___ from the past)
Myeloproliferative neoplasm from clonal hematopoietic stem cell that leads to autonomous production of RBCs not regulated by EPO. Associated with JAK2 mutation. Hyperplasia of all hematopoietic elements.
List the 3 stages of PV, and the erythropoietic pattern for each
1) Prepolycythemic - erythroid precursors abundant, maturation of cells normal 2) Polycythemic - erythroid precursors abundant, maturation of cells normal 3) Postpolycythemic - erythropoiesis ceases and there is an increase in extramedullary hematopoiesis (spleen!). Despite this EMH, stage characterized by anemia.
So PV is an unregulated increase of RBC production. How high can the lab values actually go?
Hemoglobin can exceed 20 g/dL. Hematocrit surpasses 60%. Whoa. This implies all kinds of circulation difficulties including angina pectoris, claudication, GI ulcers, thrombosis (stroke, MI)
Myeloproliferative neoplasm characterized by megakaryopoiesis, granulopoiesis, and marrow fibrosis
Stage of primary myelofibrosis presenting with thrombocytosis, hypercellular bone marrow, and megakaryocytes with atypical "cloud-like" nuclei
Prefibrotic (early stage)
Stage of primary myelofibrosis presenting with tear drop RBCs, a characteristic reticulin or collagen fibrosis in the marrow, and extramedullary hematopoiesis
Fibrotic (late stage)
Myeloproliferative neoplasm associated with JAK2 mutation or MPL mutation. Peak incidence ~70yo. In rare cases, can transform to AML.
What do the megakaryocytes distinctly look like in essential thrombocytopenia?
Uncontrolled proliferation of megakaryocytes, accompanied by recurrent episodes of thrombosis and hemorrhage?
Abnormal accumulation of mast cells in tissues
Form of mastocytosis associated with nodules on skin, usually occurring in kids that can spontaneously resolve
Cutaneous - most common is urticaria pigmentosusm
Form of mastocytosis associated with infiltration of mast cells to various organs. Can be indolent, aggressive, or leukemic. Often due to c-kit mutation, and compact aggregates of mast cells usually form
Group of syndromes characterized by peripheral blood cytopenia, marrow failure, and dysplastic morphology in one or more blood cell lineage
Myelodysplastic syndromes (up to 40% of these patients progress to have AML)
All subtypes of myelodysplastic syndromes manifest these
Refractory anemia and/or cytopenia.
No erythrocytosis, leukocytosis, or thrombocytosis.
Risk factors for developing a myelodysplastic syndrome
Hx of tx with alkylating agent or topo II inhibitor, radiation, benzene exposure, cigarette smoking, some congenital disorders
Clonal proliferation of myeloblasts in the marrow, MPO+, may have presence of Auer rods in cytoplasm?
Acute Myeloid Leukemia
What are the various classifications of AML?
1) Recurrent genetic abnormalities, 2) myelo-dysplasia related changes, 3) therapy related, 4) not otherwise categorized, 5) myeloid sarcoma, 6) related to Down Syndrome
Type of AML with genetic abnormality t(15;17) that results in PML/RAR-alpha fusion gene. Patients frequently present with DIC.
Acute promyelocytic leukemia
Extramedullary solid tumor of myeloblasts or monoblasts (called chloroma, granulocytic sarcoma, or monoblastic sarcome)
Pt presents with headache, itching, and splenomegaly. High Hgb (19.8), high WBCs (12,800), high platelets (550,000). Bone marrow displays hypercellularity. What kind of myeloproliferative disorder do they most likely have?
Polycythemia vera- uncontrolled upregulation of RBCs. Look for symptoms of hyperviscosity of blood (headache, blurry vision, itching, thrombosis/cerebrovascular accident)
An older pt presents with increasing fatigue and pancytopenia. BM shows hypercellularity and ringed sideroblasts. What is the likely diagnosis? What is the best explanation of pathogenesis?
Myelodysplastic syndrome - changes in more than one cell lineage, can display ringed sideroblasts.
Usually occurs due to a clonal stem cell defect.
60 yo pt presents with night sweats, weight loss, fatigability, discomfort in abdominal ULQ. Labs show marked leukocytosis, with a lot of mature granulocytes, myelocytes, and basophils. BM is hypercellular with mostly WBC precursors. What is your best diagnosis?
Chronic myelogenous leukemia. Forgot to mention that they found a t(9;22), with abl at the chromosomal breakpoint.
60 yo pt presents with weakness, hematuria, hepatosplenomegaly, and numerous ecchymoses. Normochromic normocytic anemia, thrombocytopenia, neutropenia, and marked leukocytosis with myeloblasts in the peripheral blood are present. What is going on?
Pt has AML, which suppresses normal hematopoiesis
48 yo pt presents with productive cough and fever. Leukocytosis and elevated leukocyte alkaline phosphatase are seen in labs. Is this CML, or a leukemoid reaction? How did you differentiate?
Leukemoid reaction! 1) LAP is elevated
Other things to look for are comparison of maturity of cells in peripheral blood vs marrow, blue cytoplasmic inclusions called Dohle bodies, and comparison of basophils